Xalkori is being approved with a companion diagnostic test that will help determine if a patient has the abnormal ALK gene, a first-of-a-kind genetic test called the Vysis ALK Break Apart FISH Probe Kit. It is the second such targeted therapy approved by the FDA this year.

This ALK gene abnormality causes cancer development and growth. About 1 percent to 7 percent of those with NSCLC have the ALK gene abnormality. Patients with this form of lung cancer are typically non-smokers. Xalkori works by blocking certain proteins called kinases, including the protein produced by the abnormal ALK gene. Xalkori is a pill taken twice a day as a single-agent treatment.

“The approval of Xalkori with a specific test allows the selection of patients who are more likely to respond to the drug” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. “Targeted therapies such as Xalkori are important options for treating patients with this disease and may ultimately result in fewer side effects.”

Xalkori’s safety and effectiveness were established in two multi-center, single-arm studies enrolling a total of 255 patients with late-stage ALK-positive NSCLC. A sample of a patient’s lung cancer tissue was collected and tested for the ALK gene abnormality prior to study enrollment. The studies were designed to measure objective response rate, the percentage of patients who experienced complete or partial cancer shrinkage. Most patients in the studies had received prior chemotherapy.

In one study, the objective response rate was 50 percent with a median response duration of 42 weeks. In another, the objective response rate was 61 percent with a median response duration of 48 weeks.

The FDA based its approval of the Vysis ALK Break Apart FISH Probe Kit on data from one of the studies.

Xalkori was reviewed under the FDA’s priority review program, which provides for an expedited six-month review of drugs that may offer major advances in treatment or that provide a treatment when no adequate therapy exists.

Xalkori is being approved under the FDA’s accelerated approval program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on an endpoint that is reasonably likely to predict a clinical benefit to patients. The program is designed to provide patients with earlier access to promising new drugs, followed by further studies to confirm the drug’s clinical benefit.

“The trend in oncology research continues towards targeted therapies,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA’s Center for Devices and Radiological Health. “This test is an example of the important role companion diagnostics play in determining that the safest and most effective treatments are promptly delivered to patients living with serious and life-threatening diseases.”

The most common side effects reported in patients receiving Xalkori included vision disorders, nausea, diarrhea, vomiting, swelling (edema), and constipation. Vision disorders included visual impairment, flashes of light, blurred vision, floaters, double vision, sensitivity to light, and visual field defects. Xalkori use has also been associated with inflammation of the lung tissue (pneumonitis), which can be life-threatening. Patients with treatment-related pneumonitis should permanently stop treatment with Xalkori. The drug should not be used in pregnant women.

In July 2011, FDA issued a draft guidance industry on the agency’s policy for reviewing a companion diagnostic and the corresponding drug therapy. The guidance is currently available for public comment.

Xalkori is marketed by New York City-based Pfizer. The Vysis ALK Break Apart FISH Probe Kit is marketed by Abbott Molecular Inc. of Des Plaines, Ill.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.